There are currently no objective measurements that can objectively evaluate the function of small nerve fibers. The currently used techniques are subjective methods that rely on the patient's collaboration and this results to a high degree of variability. This hampers the assessment of new treatments that can specifically affect the small nerve fibers in diabetic neuropathy, such as neurotrophic factors. The main objective of the present proposal is to evaluate the efficacy of nerve axon-related vasodilation measurement in quantifying the function of C nociceptive fibers and following the progression of diabetes-related dysfunction over a period of at least three years. To this end, we plan to follow up 150 diabetic patients without and with mild neuropathy and 25 healthy control subjects. All participants will be seen every 18 months for a minimum of 36 months. During each visit, neuropathy will be assessed using currently employed methods that include the assessment of the Neuropathy Symptom Score (NSS), Neuropathy Impairment Score (NIS), Vibration Perception Threshold (VPT), thermal testing and Semmes-Weinstein monofilaments. The nerve axon reflex related vasodilation, an objective measurement that can evaluate the function of the C-nociceptive fibers, will be measured during each visit. The changes in the nerve axon-related vasodilation measurement will be compared to the changes that will be observed in the currently available methods. It is hoped that this study will provide answers to the following questions: 1. What is the rate of decline of the small nerve fiber function in diabetic neuropathy? 2. Is the nerve axon-related vasodilation measurement suitable for the long term follow-up of diabetic patients who participate in clinical trials that examine the efficacy of new treatments? 3. What are the required numbers of patients and the required length of time so a clinical trial is properly powered? [unreadable] [unreadable]